Cyanine-derived compound, preparation method therefor, and application thereof

Abstract

Disclosed are a cyanine-derived compound, a preparation method therefor, and application thereof. The compound has the structure represented by formula (1), and the preparation method for the compound is further disclosed. The series of compounds of the present invention can be used as fluorescent markers for live-cell imaging analysis or flow cytometric analysis, solving problems of high toxicity, high cost and poor imaging effect of current.

What is claimed is: 
     
         1 . A cyanine derivative, having a structure represented by formula (1): 
       
         
           
           
               
               
           
         
         wherein 
         X is selected from —O— or —NH—; 
         Z is selected from —C(O)— or —(CH 2 ) m —; 
         Y −  is a biocompatible anion; 
         R 1 , R 2 , R 3 , and R 4  are selected from hydrogen, halogen, substituted or unsubstituted C 1-20  alkyl, substituted or unsubstituted C 1-20  alkoxy, substituted or unsubstituted C 6-30  aryl, C 1-20  ester or sulfonate, or any two adjacent groups of R 1 , R 2 , R 3 , and R 4 , together with a carbon atom bonded thereto, form an unsubstituted or substituted C 3-10  aliphatic ring, C 6-30  aromatic ring or C 1-30  heteroaromatic ring, wherein a substituent is selected from halogen, alkyl, and alkoxy; 
         n is an integer not less than 1; 
         k is an integer of 1-3; and 
         m is an integer of 1-6. 
       
     
     
         2 . The cyanine derivative according to  claim 1 , wherein Z is selected from —C(O)—. 
     
     
         3 . The cyanine derivative according to  claim 1  or  2 , wherein R 1 , R 2 , R 3 , and R 4  are each selected from hydrogen; n=2; X is —O—; and Y is Br. 
     
     
         4 . The cyanine derivative according to  claim 1  or  2 , wherein R 1  and R 2  are each selected from hydrogen; R 3  and R 4 , together with the carbon atom bonded thereto, form phenyl; and Y is Br. 
     
     
         5 . A preparation method for the cyanine derivative according to  claim 1 , comprising the following steps:
 step 1, performing an alkylation reaction on a compound of formula (2) as a raw material and a compound of formula (3) to obtain a compound of formula (4):   
       
         
           
           
               
               
           
         
         step 2, performing a condensation reaction on the compound of formula (4) and a compound of formula (5) to obtain a compound of formula (6): 
       
       
         
           
           
               
               
           
         
         wherein when k=1, the compound represented by formula (5) is triethyl orthoformate, and when k=2 or 3, the compound of formula (5) is: 
       
       
         
           
           
               
               
           
         
       
       and
 step 3, deacetylating the compound of formula (6) to obtain a product, and then performing an esterification reaction on the product and cyclooctetetraenoic formic acid to obtain the cyanine derivative of formula (1): 
 
       
         
           
           
               
               
           
         
       
     
     
         6 . The preparation method for the cyanine derivative according to  claim 5 , wherein a solvent used in the alkylation reaction of step 1 is toluene or acetonitrile; a solvent used in the condensation reaction of step 2 is acetic anhydride, with sodium acetate as a catalyst; and catalysts for the esterification reaction of step 3 are 2-(7-Azabenzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium hexafluorophosphate HATU and triethylamine, with DMF as a solvent. 
     
     
         7 . The preparation method for the cyanine derivative according to  claim 5 , wherein a molar ratio of the compound of formula (2) to the compound of formula (3) in the alkylation reaction is 1:1.5; a molar ratio of the compound of formula (4) to the compound of formula (5) in the condensation reaction is 2:1; and a molar ratio of the compound of formula (6) to the cyclooctatetraene formic acid in the esterification reaction is 1:2.5. 
     
     
         8 . Application of the cyanine derivative according to any one of  claims 1  to  4  as a mitochondrial fluorescent marker for live-cell imaging analysis or flow cytometric analysis.